Chemical and Functional Properties of Food Saccharides

© 2004 by CRC Press LLC
17.2.3 METABOLISM AND TOXICOLOGY 11–13
The fate of CDs in the mammal organisms is crucial for applications of CDs in the
pharmaceutical and food industries. CDs orally administered with pharmaceuticals
or food are either free CDs or CD inclusion complexes containing a drug, flavor, or
other guest substance. Under physiological conditions, the inclusion complexes
undergo instant dissociation in the gastrointestinal tract. Therefore, only the absorption
of free CDs deserves attention. Summarizing the available data and experimental
observations, the following conclusions can be drawn. CDs are relatively large
molecules with strongly hydrophilic outer surfaces. They are true carriers bringing
hydrophobic guests into solution, keeping them in solution, and transporting them
to the lipophilic cell membrane. After delivery of the guest to the cell, because the
cell has higher affinity to the guest than to the CD, the latter remains in the aqueous
phase. Only an insignificant amount of orally administered CD is absorbed from the
intestinal tract in the intact form. Eventual CD-elicited toxic phenomena might result
from the solubilizing effect of CDs facilitating migration of insoluble, nonabsorbable
toxic compounds such as fused-ring aromatic hydrocarbons and pesticides to and
throughout the organism.
In contrast to starch which is metabolized in the small intestine, the preponderant
part of orally administered CD is metabolized by the colon microflora. The maximum
intensity of starch metabolism is achieved within the first two hours. Similar to
starch, acyclic maltodextrins, maltose, and glucose, the primary metabolites, are
absorbed, metabolized, and finally excreted in the form of CO 2 and H 2 O. The apogee
in metabolism of CDs is observed within the sixth to eighth hour after their uptake.
The metabolism of α-CD is the slowest and that of γ-CD the fastest. Chemically
modified CDs may be resistant to enzymatic degradation. Thus, methylated and
hydroxypropylated CDs and perhaps all other more or less substituted CD derivatives
can be absorbed from the intestinal tract to a quite considerable extent and enter
circulation.
On parenteral administration, all CDs can interact with the components of the
cell membranes, but the extent of this interaction may be entirely different. This
cell-damaging effect can be illustrated by the CD concentration-dependent hemolysis
of erythrocytes and decrease in the luminescence of Escherichia coli suspensions.
More hydrophobic but still well-soluble CD derivatives such as dimethyl β-CD
exerted the strongest effect. The cell-damaging effect from CD is caused by their
complexation of cell wall components such as cholesterol and phospholipids. Therefore,
among all CDs, β-CD, and particularly its more hydrophobic derivatives such
as dimethyl β-CD, show the strongest cell-membrane damaging effect. γ-CD and its
derivatives are less toxic, as due to the diameter of its cavity, affinity to cholesterol
and phospholipids is lower. The immediate toxic consequence can be avoided when
CDs are administered at a rate that maintains their actual concentration below the
hemolytic threshold concentration (slow infusion, absorption from the intestinal
tract, or through the skin). However, the toxic effect to kidneys cannot be eliminated.
Parenteral administration of β-CD is impossible because it forms the most stable
cholesterol/CD complex, which accumulates in the kidneys and destroys cells.
Apparently, γ-CD is free from this noxious property. γ-CD is well soluble and does